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Abstract

Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis.

M O'Donnell, R J Garippa, N Rinaldi, W M Selig, J E Tocker, S A Tannu, M A Wasserman, A Welton and D R Bolin
Journal of Pharmacology and Experimental Therapeutics September 1994, 270 (3) 1289-1294;
M O'Donnell
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R J Garippa
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N Rinaldi
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W M Selig
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J E Tocker
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S A Tannu
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M A Wasserman
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A Welton
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D R Bolin
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Abstract

Studies were conducted to compare the effect of native vasoactive intestinal peptide (VIP), Ro 25-1553 (a cyclic peptide analog of VIP) and salbutamol (a beta2-adrenoceptor agonist) on antigen-induced pathophysiological effects in the guinea pig. Ro 25-1553 and salbutamol (0.01-1.0 microM) prevented antigen-induced contractions of the guinea pig trachea in vitro with IC50 values of 0.07 and 0.05 microM, respectively. VIP (0.01-1.0 microM) had no effect on antigen-induced tracheal contractions. Aerosolized Ro 25-1553 and salbutamol were equipotent in preventing antigen-induced increases in guinea pig lung resistance (IC50 value = 0.0001%), whereas aerosolized VIP (0.1%) was ineffective. Ro 25-1553 (0.1-100 micrograms), instilled intratracheally 2 min before the antigen challenge of buffer-perfused lungs from sensitized guinea pigs, produced a dose-dependent inhibition of bronchoconstrictor, vasoconstrictor and edemagenic responses, whereas intratracheal VIP (100 micrograms) had no effect. Intratracheal salbutamol (0.1-100 micrograms) inhibited antigen-induced responses in a manner comparable to Ro 25-1553. Lung inflammation was assessed as leukocyte accumulation in bronchoalveolar lavage fluid after the antigen provocation. Aerosolized antigen-induced bronchoalveolar lavage eosinophilia (13-fold increase over saline controls) at 6 hr after challenge was prevented in a concentration-dependent manner by pretreatment with nebulized Ro 25-1553 and salbutamol, but not by pretreatment with native VIP. These results indicate that Ro 25-1553 suppresses various pathophysiological features associated with pulmonary anaphylaxis and asthma, including airway reactivity, edema formation and granulocyte accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 270, Issue 3
1 Sep 1994
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Abstract

Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis.

M O'Donnell, R J Garippa, N Rinaldi, W M Selig, J E Tocker, S A Tannu, M A Wasserman, A Welton and D R Bolin
Journal of Pharmacology and Experimental Therapeutics September 1, 1994, 270 (3) 1289-1294;

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Abstract

Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis.

M O'Donnell, R J Garippa, N Rinaldi, W M Selig, J E Tocker, S A Tannu, M A Wasserman, A Welton and D R Bolin
Journal of Pharmacology and Experimental Therapeutics September 1, 1994, 270 (3) 1289-1294;
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